Living Donor Liver Transplantation In Children Research Articles

Prediction of early recovery of graft function after living donor liver transplantation in children

For end-stage liver disease in children, living donor liver transplantation (LDLT) is often the important standard curative treatment. However, there is a lack of research on early recovery of graft function after pediatric LDLT. This is a single-center, ambispective cohort study. We collected the demographic and clinicopathological data of donors and recipients, and determined the risk factors of postoperative delayed recovery of hepatic function (DRHF) by univariate and multivariate Logistic analyses. 181 cases were included in the retrospective cohort and 50 cases in the prospective cohort. The incidence of DRHF after LDLT in children was 29.4%, and DRHF could well evaluate the early recovery of graft function after LDLT. Through Logistic analyses and AIC score, preoperative liver function of donors, ischemia duration level of the liver graft, Ln (Cr of recipients before operation) and Ln (TB of recipients on the 3rd day after operation) were predictive indicators for DRHF after LDLT in children. Using the above factors, we constructed a predictive model to evaluate the incidence of postoperative DRHF. Self-verification and prospective internal verification showed that this prediction model had good accuracy and clinical applicability. In conclusion, we pointed many risk factors for early delayed recovery of graft function after LDLT in children, and developed a visual and personalized predictive model for them, offering valuable insights for clinical management.

Association of different central venous pressure levels with outcome of living-donor liver transplantation in children under 12years.

Pediatric liver transplantation is an important modality for treating biliary atresia. The overall survival (OS) rate of pediatric liver transplantation has significantly improved compared with that of 20years ago, but it isstill unsatisfactory. The anesthesia strategy of maintaining low central venous pressure (CVP) has shown a positive effect on prognosis in adult liver transplantation. However, this relationship remains unclear in pediatric liver transplantation. Thus, this study was conducted to review the data of pediatric living-donor liver transplantation to analyze the associations of different CVP levels with the prognosis of recipients. This was a retrospective study and the patients were divided into two groups according to CVP levels after abdominal closure: low CVP (LCVP) (≤ 10cmH2O, n = 470) and high CVP (HCVP) (> 10cmH2O, n = 242). The primary outcome measured in the study was the overall survival rate. The secondary outcomes included the duration of mechanical ventilation in the intensive care unit (ICU), length of stay in the ICU, and postoperative stay in the hospital. Patient demographic and perioperative data were collected and compared between the two groups. Kaplan-Meier curves were constructed to determine the associations of different CVP levels with the survival rate. In the study, 712 patients, including 470 in the LCVP group and 242 in the HCVP group, were enrolled. After propensity score matching, 212 pairs remained in the group. The LCVP group showed a higher overall survival rate than the HCVP group in the Kaplan-Meier curves and multivariate Cox regression analyses (P = 0.018), and the HCVP group had a hazard ratio of 2.445 (95% confidence interval, 1.163-5.140). This study confirmed that a low-CVP level at the end of surgery is associated with improved overall survival and a shorter length of hospital stay.

Progress in living donor liver transplantation for biliary atresia and challenges faced: A thirty-year single institutional experience

BackgroundBiliary atresia (BA) is the most common indication for liver transplantation in the pediatric population, and living donor liver transplantation (LDLT) and deceased donor liver transplantation (DDLT) have been established as a radical treatment for BA .The aim of this study was to clarify the long term outcomes and risk factors affecting the LDLT outcomes, as well as the challenges faced. MethodsBetween 1990 and 2019, 666 BA patients underwent LDLT in our institution and were enrolled in this study. Data regarding the recipient's age, anatomic findings of the biliary tree at Kasai's portoenterostomy, basic characteristics at transplantation, transplant profiles, donor characteristics, and outcomes of LDLT were analyzed. ResultsThe 1-, 5-, 10-, 15-, 20-, and 25-year graft survival rates of BA patients who underwent LDLT were 88.1%, 85.4%, 81.5%, 78.9%, 76.6%, and 75.5%, respectively. The transplant era, age at transplantation, ABO incompatible transplant, and presence of pulmonary vascular complications were identified as significant risk factors for overall graft survival. When the study period was divided into the first (1990–1999) and second (2000–2019) phases and re analyzed, the outcomes of ABO-incompatible transplants and LDLT for adult BA patients remained inferior to others in the second phase. The 20-year graft survival rate in patients who underwent re transplantation in the second phase was 54.2%. ConclusionsThe outcomes of LDLT in children are generally good, but the immunosuppression procedures need to be further improved for ABO-incompatible cases in the future. Further improvements in LDLT results for adult patients and re transplantation remain challenges to be addressed in this field, and future attempts, including revision to the organ allocation system of deceased donors, are necessary. Level of evidenceLevel III (case control study).

Therapeutic potential of living donor liver transplantation from heterozygous carrier donors in children with propionic acidemia

BackgroundCurrent world experience regarding living donor liver transplantation (LDLT) in the treatment of propionic acidemia (PA) is limited, especially in terms of using obligate heterozygous carriers as donors. This study aimed to evaluate the clinical outcomes of LDLT in children with PA.MethodsFrom November 2017 to January 2020, 7 of the 192 children who underwent LDLT at our institution had been diagnosed with PA (median age, 2.1 years; range, 1.1–5.8 years). The primary indication for transplantation was frequent metabolic decompensations in 6 patients and preventative treatment in 1 patient. Of the seven parental living donors, six were genetically proven obligate heterozygous carriers.ResultsDuring a median follow-up of 23.9 months (range, 13.9–40.2 months), all patients were alive with 100% allograft survival, and no severe transplant-related complications occurred. In the case of liberalized protein intake, they did not suffer metabolic decompensation or disease-related complications and made progress in neurodevelopmental delay and body growth, as well as blood and urinary metabolite levels. In one patient with pre-existing mild dilated cardiomyopathy, her echocardiogram results completely normalized 13.8 months post-transplant. All living donors recovered well after surgery, with no metabolic decompensations or procedure-related complications. Western blotting revealed that the hepatic expressions of PCCA and PCCB in one of the heterozygous donors were comparable to those of the normal healthy control at the protein level.ConclusionsLDLT using partial liver grafts from asymptomatic obligate heterozygous carrier donors is a viable therapeutic option for selected PA patients, with no negative impact on donors’ and recipients' clinical courses.

Neurological complications after living-donor liver transplantation in children

AimLiver transplantation (LT) has been used as a definitive management for children with end-stage liver disease or acute liver failure. Living-donor LT (LDLT) has been a common type of LT performed in Asian countries, including Japan, where deceased donors are rarely available. However, the neurological complications (NCs) associated with LDLT remain unknown. The purpose of this study was to clarify the characteristics of NCs in children after LDLT. MethodsThis study is a retrospective observational study carried out at a tertiary children’s hospital in Japan. We studied children who had undergone LDLT between January 2001 and January 2020. ResultsWe examined 602 cases of LT, of which 559 were LDLT cases (92.9%). NCs after LT were present in 21 cases (3.8%). The most common neurological symptoms were seizure (n = 17), whereas disturbance of consciousness without seizure was observed in four cases. The frequency of NCs for each of the indications was 12.2% for fulminant hepatic failure, 6.5% for metabolic liver disease, and 0.7% for cholestatic liver disease. InterpretationWe report the characteristics of NCs after LDLT in children. The frequency of NCs after LT was high in cases of fulminant hepatic failure and metabolic diseases, who might have had neurological symptoms or impaired consciousness before LT.

Outcome for Pediatric Recipients of Macrosteatotic Liver Grafts From Living Donors.

In deceased donor liver transplantation, a donor liver with moderate (>30%) macrosteatosis used to be considered inappropriate for grafting. We examined the outcomes of children who underwent living donor liver transplantation (LDLT) at the National Center for Child Health and Development whose donor livers had moderate-to-severe macrosteatosis. Twelve children were enrolled who had received a moderate-to-severe macrosteatotic liver graft and underwent liver biopsy soon after LDLT. The primary diseases were biliary atresia in 7 patients, acute liver failure in 3 patients, glycogen storage disease type 1 in 1 patient, and primary sclerosing cholangitis in 1 patient. Median age was 11 months. There were 4 recipients who received grafts from their fathers, and 8 received grafts from their mothers. Median donor age was 35.5 years. We compared the degree of donor liver steatosis with the results of graft liver biopsies that were collected 4-105 days after LDLT. The levels of donor liver macrovesicular steatosis were moderate (34%-66%) in 9 patients and severe (>66%) in 3 patients. The nonalcoholic fatty liver disease activity score was 3 in 7 patients and 4 in 5 patients. Shortly after LDLT, 11 of 12 patients showed improvement in steatosis compared with the donor livers. One biopsy specimen taken 22 days after LDLT showed 60% macrosteatosis, which was the same as that in the donor liver. However, this patient was alive and well 6 years after LDLT. One patient died after LDLT because of infection and respiratory failure. The levels of steatosis of the donor liver grafts improved soon after LDLT in children, and the outcomes of children receiving a moderate-to-severe macrosteatotic liver from their parents were excellent.

Pilot study of living donor liver transplantation for patients with hepatocellular carcinoma exceeding Milan Criteria (Barcelona Clinic Liver Cancer extended criteria).

A subset of patients with hepatocellular carcinoma (HCC) beyond Milan criteria might obtain acceptable survival outcomes after liver transplantation. Living donor liver transplantation (LDLT) has emerged as a feasible alternative to overcome the paucity of donors. In 2001, we started a protocol for LDLT in Child A-B patients with HCC fulfilling a set of criteria-the Barcelona Clinic Liver Cancer (BCLC) expanded criteria-that expanded the conventional indications of transplantation: 1 tumor ≤ 7 cm, 5 tumors ≤ 3 cm, and 3 tumors ≤ 5 cm without macrovascular invasion or downstaging to Milan after locoregional therapies. We present a prospective cohort of 22 patients with BCLC extended indications based on size/number (n = 17) or downstaging (n = 5) treated with LDLT between 2001 and 2014. Characteristics of the patients were as follows: median age, 57 years old; males/female, n = 20/2; Child-Pugh A/B, n = 16/6; and alpha fetoprotein < 100 ng/mL, n = 21. Twelve patients received neoadjuvant locoregional therapies. At the time of transplantation, 12 patients had HCC staging beyond Milan criteria and 10 within. Pathological reports showed that 50% exceeded BCLC expanded criteria. Perioperative mortality was 0%. After a median follow-up of 81 months, the 1-, 3-, 5-, and 10-year survival was 95.5%, 86.4%, 80.2%, and 66.8%, respectively. Overall, 7 patients recurred (range, 9-108 months), and the 5-year and 10-year actuarial recurrence rates were 23.8% and 44.4%, respectively. In conclusion, a proper selection of candidates for extended indications of LDLT for HCC patients provide survival outcomes comparable to those obtained within the Milan criteria, but these results need confirmation. Liver Transplantation 24 369-379 2018 AASLD.

Predictive Value of Intraoperative Troponin I Elevation in Pediatric Living Donor Liver Transplant Recipients With Biliary Atresia.

Pediatric living donor liver transplantation is associated with slight alteration in cardiac enzymes without ongoing acute cardiac injury, but available information about the significance of these changes is limited. The aims of this study were to analyze the link between the anomalies of intraoperative serum cardiac troponin I (cTnI) and acute lung injury during the first week after liver transplantation. In this retrospective study, 123 children suffering from biliary atresia were enrolled. Several perioperative variables, particularly cTnI before operation and at 30 minutes of neohepatic phase were recorded. Sixty-four recipients were divided into high cTnI group (≥0.07 ng/mL) and 59 recipients composed normal cTnI group (<0.07 ng/mL). The clinical data between 2 groups were compared and the association between serum cTnI level and acute lung injury after living donor liver transplantation were evaluated by univariate and multivariate logistic regression analyses. The percentage of acute lung injury after pediatric living donor liver transplantation among high cTnI group and normal cTnI group was 34.3% and 11.9%, respectively. Intratransplant cTnI ≥ 0.07 ng/mL (odds ratio [OR], 3.475; 95% confidence interval [CI], 1.114-10.842) was the risk factors for acute lung injury after transplantation. The value of cTnI showed the close correlation with preoperative bilirubin (OR, 1.005; 95% CI, 1.002-1.008) and pretransplant albumin (OR, 0.915; 95% CI, 0.849-0.986). Intraoperative cTnI elevation was the significant prognostic risk factor in acute lung injury after pediatric living-donor liver transplantation for children with biliary atresia. And the value of cTnI was associated with preoperative bilirubin and albumin level.

Concentration of CD34/CD45 Positive Cells in Peripheral Blood of Pediatric Patients before and after Living Donor Liver Transplantation

Introduction: The number of bone marrow stem cells (BMSC) can increase in peripheral blood as a response to inflammation, tissue damage and different stress signals. It has been shown that host BMSC can be detected in transplanted liver. Probably the stem cells can influence the liver regeneration but the exact role of the cells is not clear yet. The aim of the study was to determine the relationship between concentration of CD34/CD45+ cells in peripheral blood and plasma level of biomarkers of inflammation and biochemical parameters following living donor liver transplantation (LDLT) and partial liver resection. Methods: The study included 15 pairs of recipients (aged from 4 to 60 months, 8 male/7 female) and adult living-related liver donors (29±5 years, 6 male/9 female). All pediatric patients had liver cirrhosis caused by congenital and inherited diseases of hepatobiliary system. The procedures in donors included left lateral sectorectomy, in recipients - hepatectomy, orthotopic implantation of left lateral sector, biliary reconstruction by hepaticojejunostomy. All recipients received 2- or 3-drug immunosuppressive therapy including tacrolimus. Concentration of CD34/CD45+ cells were measured by flow cytometry, plasma level of C-reactive protein (CRP) was determined by immunoturbidimetry, soluble ligand of CD40 (sCD40L), soluble CD30 (sCD30) and neopterin - by ELISA. Results: Before LDLT concentration of CD34/CD45+ cells in venous blood of pediatric patients was higher than in adult healthy donors. After LDLT number of CD34/CD45+ cells did not change in peripheral blood of liver recipients. Partial liver resection in donors did not cause significant changes in number of CD34/CD45+ cells in blood. Before LDLT in recipients CD34/CD45+ cells concentration did not correlate (Spearman's test) with sex, age, weight, height, sCD40L (co-stimulatory molecule of T-lymphocyte activation), sCD30 (a marker of T-helper cells 2 type activation), neopterin, routine biochemical parameters such as bilirubin, total protein, ALT, AST and GGT activity and white blood cells count but correlated (p< 0,05) with CRP (rs=-0,69), albumin (rs=0,64), hemoglobin (rs=0,70) levels and red blood cells count (RBC) (rs=0,73). Conclusion: Presented data suggests that neither LDLT in children nor liver resection in healthy adult donors has significant influence on number of CD34/CD45+ cells in peripheral blood but the stem cells concentration has relationship with inflammatory activity, concentration of albumin, hemoglobin and RBC.

Analysis of early-stage infection risk factors after living donor liver transplantation in 25 children

Living donor liver transplantation (LDLT), which was first demonstrated in 1989, has now been widely used to cure many late-stage hepatic diseases and has achieved huge success, especially in the pediatric field. However, accumulated studies indicate that early-stage infection after LDLT is the main cause leading to its failure and the death of the patient. Here, we retrospectively analyzed 25 cases (from 2006 to 2009) of infections of children in our hospital, underwent LDLT and their correlated factors. To identify the factors most closely related to early stage infection, we categorized early stage infection levels as either mild, moderate or severe and we compared their related risk factors, including total length of stay in hospital (TLSH), length of stay in the intensive care unit (LSI), duration of catheterization (DC), length of pre-/post-operative antimicrobial agent application, length of immuno-suppressant agent application (LISA) and underlying diseases postoperatively. The results revealed the following. (i) Of 25 patients, 24 recipients were infected to various extents: 6 cases of mild infection, 14 cases of moderate infection and 4 cases of severe infection (one patient died). (ii) TLSH, LSI and durations of preoperative (DPAA) and postoperative (DPOAA) antimicrobial agent application were statistically different between the severe and moderate infection groups (P = 0.03 (TLSH), 0.004 (LSI), 0.003 (LAPP), 0.005 (DPOAA). (iii) Between the severe and mild infection groups, the TLSH (P = 0.016), LSI (P = 0.015), DAPP (P = 0.007) and DPOAA (P = 0.001) were also significantly different. (iv) In the case of LISA, only methylprednisolone (P = 0.01) and the calcineurin inhibitor ciclosporin A (P = 0.009) showed statistically significant differences between the moderate and mild infection groups. (v) Biliary atresia is the predominant underlying liver disease. (vi) In contrast to previous findings, there was no significant difference in DC among the three infection groups. (vii) Of all the 25 patients, 24 survive till now and the only one died was diagnosed as portal vein thrombosis (PVT) combined with high white blood count (>30 x 109/l) in venous blood. DPAA, DPOAA and biliary atresia are the risk factors most closely related to infection during liver transplantation in children, an observation worthy of future investigation. To avoid long term DPAA and long term DPOAA induced early severe infection, nosocomial infection control and drug resistant bacteria monitoring are worthy to be concerned after LDLT in children. Key words: Living donor liver transplantation, risk factor, children.

Infections after Living Donor Liver Transplantation in Children

The aim of this study was to evaluate the infectious complications after living donor liver transplantation (LDLT) in children. We enrolled 95 children (38 boys and 57 girls) who underwent LDLT from 1994 to 2004. The median age was 22 months (range, 6 months to 15 yr). We retrospectively investigated the proven episodes of bacterial, viral, and fungal infection. There occurred 150 infections in 67 (70%) of 95 patients (1.49 infections/patient); 74 in 43 patients were bacterial, 2 in 2 were fungal, and 74 in 42 were viral. The most common sites of bacterial infection were the bloodstream (33%) and abdomen (25%). Most of the bacterial infections occurred within the first month after LDLT. Bacterial and fungal infections did not result in any deaths. The most common causes of viral infection were Epstein-Barr virus in 37 patients and cytomegalovirus in 18. Seven of the 14 deaths after LDLT were associated with viral infection. Our study suggests that infection is one of the important causes of morbidity and mortality after LDLT. Especially careful monitoring and management of viral infections is crucial for improving the outcome of LDLT in children.

Quality of Life and Problems Affecting Recipients More Than 10 Years After Living Donor Liver Transplantation

Background We initiated living donor liver transplantation (LDLT) in 1991, allowing us to examine issues related to long-term survival. The aim of this study was to review the long-term outcomes of LDLT in children. Patients and Methods We performed 116 LDLT from 1991 to present, including 17 recipients who survived >10 years. They were evaluated for growth, immunosuppressive therapy, complications, and quality of life (QOL). Results The average age at LDLT was 5.4 years (range, 6 months to 17 years), with a present average age of 17.2 years (range, 11–28 years). At the time of LDLT, 6 recipients had growth retardation with body weights low for age by 2 standard deviations (SD). However, 4 of 6 recipients who underwent LDLT before age of 2 years caught up, reaching average heights and body weights for their ages. Among 6 recipients who were diagnosed with acute rejections by biopsy >5 years after LDLT, 5 improved after steroid pulse therapy. One recipient with a steroid-resistant acute rejection was administered deoxyspergualin after steroids. Chronic rejection was not observed in this series. One recipient has not required immunosuppressive therapy for >4 years with a good present condition. Conclusion The majority of LDLT recipients achieved a good QOL during long-term survival; they are pursuing normal studies.

Transileocolic venous balloon dilatation for the management of primary and recurrent portal venous stenosis after living donor liver transplantation in children

Portal venous stenosis is relatively a rare complication after liver transplantation in children and it sometimes leads to life threatening event due to gastrointestinal bleeding or graft failure. Recently, balloon dilatation has been widely accepted as a treatment of choice for the management of portal venous stenosis. The purpose of this study was to evaluate the feasibility of transileocolic venous balloon dilatation for the management of primary and recurrent portal venous stenosis after living donor liver transplantation (LDLT) in children. The records of 57 pediatric liver transplants were retrospectively reviewed. Nine patients (15.8%) with portal venous stenosis were identified. Seven symptomatic children with portal venous stenosis underwent balloon dilatation. Two approaches were employed for balloon dilatation; the transileocolic venous approach and the percutaneous transhepatic approach. In patients with recurrent stenosis, careful follow-up was carried out while they were asymptomatic. Twelve balloon dilatations were performed in seven children with primary or recurrent portal venous stenoses. The initial technical success rate was 91.7% (11/12), while 6 out of 12 (50.0%) procedures resulted in recurrent stenosis. Five out of six recurrent stenoses required repeated balloon dilatation. The clinical success rate of balloon dilatation in our study was 85.7% (6/7). Other than recurrent stenosis, two procedure-related complications occurred. In conclusion, transileocolic venous balloon dilatation was a safe and effective procedure for portal venous stenosis after LDLT in children.

Split-liver transplantation eliminates the need for living-donor liver transplantation in children with end-stage cholestatic liver disease.

End-stage cholestatic liver disease (ESCLD) is the main indication for liver replacement in children. Pediatric cadaver-organ-donor shortage has prompted the most important evolutions in the technique of liver transplantation, in particular living-donor liver transplantation (LDLT) and split-liver transplantation (SLT). Between November 1997 and June 2001, 127 children with ESCLD were evaluated for liver transplantation, and 124 underwent 138 liver transplantations after a median time of 40 days. Causes of liver disease were congenital biliary atresia (n=96), Alagille's syndrome (n=12), Byler's disease (n=8), and other cholestatic diseases (n=8). Ninety (73%) patients received a split-liver graft, 28 (23%) a whole liver, and 6 (4%) a reduced-size liver. Overall 2- and 4-year patient survival rates were 93% and 91%, respectively; the 2- and 4-year graft-survival rates were 84% and 80%, respectively. In split-liver recipients, 4-year patient and graft-survival rates were 91% and 83%, respectively; these were 93% and 78%, respectively, in whole-liver recipients and 67% and 63%, respectively, in reduced-size liver recipients. Retransplantation rate was 11%, whereas mortality rate was 8%. Overall incidence of vascular and biliary complication were 16% and 27%, respectively. SLT can provide liver grafts for children with ESCLD with an outcome similar to the one reported following LDLT, eliminating mortality while they are on a transplantation wait list. The need for pediatric LDLT should be reevaluated and programs of SLT strongly encouraged and supported at a national and international level.

Living-donor liver transplantation in children.

With evolution of surgical technique, advances in immunosuppression, and better understanding of pre- and post-operative care, the 1-yr survival rate after liver transplantation in children has reached 85-90%. As a result, a greater number of patients have been listed for transplantation and waiting times have lengthened. Innovative techniques such as reduced-size, split, and living-donor liver transplantation are being applied more often to decrease long waiting times and reduce associated morbidity and mortality. In this review, living donor liver transplantation in pediatrics is described. Special issues, such as donor and recipient selection, surgical procedures in donors and recipients, and ethical issues, are discussed.

Living-donor liver transplantation in children.

Living-related liver transplantation (LRLT) for paediatric recipients was developed 10 years ago to overcome the high mortality on the waiting list. Since then, liver transplantation programs around the world have begun to employ this method with encouraging results. This review describes the actual status of LRLT in children, aspects of donor selection, donor risks, and surgical technique, as well as an update of the results of the leading LRLT programs in the world. The donor operation has matured to the stage of being a standardised, teachable procedure with a low risk of morbidity or mortality. However, there is a percentage of potential donations that have to be declined for medical or socio-psychological reasons. LRLT provides grafts of excellent quality and short cold ischemic times. A major advantage is the fact that the optimal moment for the transplantation procedure can be chosen. Together with split-liver techniques, LRLT has a positive effect on the general situation of the paediatric waiting list for liver transplantation, with a reduction of pre-transplant mortality to nearly 0%.